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Q8J025 (APCD1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified December 14, 2011. Version 68. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein APCDD1
Alternative name(s):
Adenomatosis polyposis coli down-regulated 1 protein
Gene names
Name:APCDD1
Synonyms:DRAPC1
ORF Names:FP7019
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length514 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Negative regulator of the Wnt signaling pathway. Inhibits Wnt signaling in a cell-autonomous manner and functions upstream of beta-catenin. May act via its interaction with Wnt and LRP proteins. May play a role in colorectal tumorigenesis. Ref.1 Ref.5

Subunit structure

Homodimer. Interacts with LRP5 and WNT3A. Ref.5

Subcellular location

Cell membrane; Single-pass type I membrane protein Ref.5.

Tissue specificity

Abundantly expressed in heart, pancreas, prostate and ovary. Moderately expressed in lung, liver, kidney, spleen, thymus, colon and peripheral lymphocytes. Abundantly expressed in both the epidermal and dermal compartments of the hair follicle. Present in scalp skin Highly expressed in the hair follicle dermal papilla, the matrix, and the hair shaft (at protein level). Ref.1 Ref.5

Induction

Target gene of the Wnt/Beta-catenin pathway, transcriptionally regulated by the CTNNB1/TF7L2 complex. Ref.1

Post-translational modification

N-Glycosylated. Ref.5

Involvement in disease

Defects in APCDD1 are a cause of hypotrichosis type 1 (HYPT1) [MIM:605389]. A rare form of non-syndromic hereditary hypotrichosis without characteristic hair shaft anomalies. Affected individuals typically show normal hair at birth, but hair loss and thinning of the hair shaft start during early childhood and progress with age. Ref.5

Sequence similarities

Belongs to the APCDD1 family.

Sequence caution

The sequence AAQ04816.1 differs from that shown. Reason: Frameshift at position 133.

The sequence BAG64192.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8J025-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q8J025-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MKRRCSCGGGGGHCSSERRRTRPEAEGRARAQLPGHQIGARRAGGPRAGLEM
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2626 Potential
Chain27 – 514488Protein APCDD1
PRO_0000227520

Regions

Topological domain27 – 492466Extracellular Potential
Transmembrane493 – 51220Helical; Potential
Topological domain513 – 5142Cytoplasmic Potential

Amino acid modifications

Glycosylation1001N-linked (GlcNAc...) Potential
Glycosylation1681N-linked (GlcNAc...) Potential
Glycosylation3191N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence11M → MKRRCSCGGGGGHCSSERRR TRPEAEGRARAQLPGHQIGA RRAGGPRAGLEM in isoform 2.
VSP_039542
Natural variant91L → R in HYPT1; dominant-negative mutant that perturbs the translational processing from the endoplasmic reticulum to the plasma membrane. Ref.5
VAR_063497
Natural variant1501V → I.
Corresponds to variant rs3748415 [ dbSNP | Ensembl ].
VAR_050667

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified March 1, 2003. Version 1.
Checksum: 75DA7B8B38E3FFE5

FASTA51458,797
        10         20         30         40         50         60 
MSWPRRLLLR YLFPALLLHG LGEGSALLHP DSRSHPRSLE KSAWRAFKES QCHHMLKHLH 

        70         80         90        100        110        120 
NGARITVQMP PTIEGHWVST GCEVRSGPEF ITRSYRFYHN NTFKAYQFYY GSNRCTNPTY 

       130        140        150        160        170        180 
TLIIRGKIRL RQASWIIRGG TEADYQLHNV QVICHTEAVA EKLGQQVNRT CPGFLADGGP 

       190        200        210        220        230        240 
WVQDVAYDLW REENGCECTK AVNFAMHELQ LIRVEKQYLH HNLDHLVEEL FLGDIHTDAT 

       250        260        270        280        290        300 
QRMFYRPSSY QPPLQNAKNH DHACIACRII YRSDEHHPPI LPPKADLTIG LHGEWVSQRC 

       310        320        330        340        350        360 
EVRPEVLFLT RHFIFHDNNN TWEGHYYHYS DPVCKHPTFS IYARGRYSRG VLSSRVMGGT 

       370        380        390        400        410        420 
EFVFKVNHMK VTPMDAATAS LLNVFNGNEC GAEGSWQVGI QQDVTHTNGC VALGIKLPHT 

       430        440        450        460        470        480 
EYEIFKMEQD ARGRYLLFNG QRPSDGSSPD RPEKRATSYQ MPLVQCASSS PRAEDLAEDS 

       490        500        510 
GSSLYGRAPG RHTWSLLLAA LACLVPLLHW NIRR 

« Hide

Isoform 2 [UniParc].

Checksum: 40C79B378480EAAF
Show »

FASTA56564,178

References

« Hide 'large scale' references
[1]"Isolation of a novel human gene, APCDD1, as a direct target of the b-catenin/T-cell factor 4 complex with probable involvement in colorectal carcinogenesis."
Takahashi M., Fujita M., Furukawa Y., Hamamoto R., Shimokawa T., Miwa N., Ogawa M., Nakamura Y.
Cancer Res. 62:5651-5656(2002) [PubMed: 12384519] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, INDUCTION.
Tissue: Colon.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Neuroepithelioma and Thymus.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Ovary.
[4]"Large-scale cDNA transfection screening for genes related to cancer development and progression."
Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X., Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X. expand/collapse author list , Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.
Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004) [PubMed: 15498874] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 18-514.
[5]"APCDD1 is a novel Wnt inhibitor mutated in hereditary hypotrichosis simplex."
Shimomura Y., Agalliu D., Vonica A., Luria V., Wajid M., Baumer A., Belli S., Petukhova L., Schinzel A., Brivanlou A.H., Barres B.A., Christiano A.M.
Nature 464:1043-1047(2010) [PubMed: 20393562] [Abstract]
Cited for: VARIANT HYPT1 ARG-9, CHARACTERIZATION OF VARIANT HYPT1 ARG-9, GLYCOSYLATION, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, SUBUNIT, INTERACTION WITH LRP5 AND WNT3A.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB056722 mRNA. Translation: BAC15563.1.
AB104887 mRNA. Translation: BAC65165.1.
AK300743 mRNA. Translation: BAG62412.1.
AK303076 mRNA. Translation: BAG64192.1. Different initiation.
BC053324 mRNA. Translation: AAH53324.1.
AF461902 mRNA. Translation: AAQ04816.1. Frameshift.
IPIIPI00216332.
IPI00939369.
RefSeqNP_694545.1. NM_153000.4.
UniGeneHs.293274.

3D structure databases

ProteinModelPortalQ8J025.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP-56190N.
IntActQ8J025. 1 interaction.
STRINGQ8J025.

PTM databases

PhosphoSiteQ8J025.

Polymorphism databases

DMDM74728445.

Proteomic databases

PRIDEQ8J025.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000355285; ENSP00000347433; ENSG00000154856.
ENST00000423585; ENSP00000404930; ENSG00000154856.
GeneID147495.
KEGGhsa:147495.
UCSCuc002kom.2. human.

Organism-specific databases

CTD147495.
GeneCardsGC18P010444.
H-InvDBHIX0014332.
HGNCHGNC:15718. APCDD1.
HPAHPA014468.
MIM605389. phenotype.
607479. gene.
neXtProtNX_Q8J025.
Orphanet55654. Hypotrichosis simplex.
PharmGKBPA24876.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG08479.
GeneTreeENSGT00390000000925.
HOVERGENHBG060356.
InParanoidQ8J025.
OMACHTEAVA.
OrthoDBEOG4548ZM.
PhylomeDBQ8J025.

Gene expression databases

ArrayExpressQ8J025.
BgeeQ8J025.
CleanExHS_APCDD1.
GenevestigatorQ8J025.
GermOnlineENSG00000154856. Homo sapiens.

Family and domain databases

ProtoNetSearch...

Other

NextBio85626.
SOURCESearch...

Entry information

Entry nameAPCD1_HUMAN
AccessionPrimary (citable) accession number: Q8J025
Secondary accession number(s): B4DUQ0, B4DZT0, Q71M25
Entry history
Integrated into UniProtKB/Swiss-Prot: March 7, 2006
Last sequence update: March 1, 2003
Last modified: December 14, 2011
This is version 68 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

Human chromosome 18

Human chromosome 18: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families